Rating scales and biomarkers for CAG-repeat spinocerebellar ataxias: Implications for therapy development

Spinocerebellar ataxias (SCAs) are a group of dominantly-inherited cerebellar ataxias, among which CAG expansion-related SCAs are most common. These diseases have very high penetrance with defined disease progression, and emerging therapies are being developed to provide either symptomatic or disease-modifying benefits. In clinical trial design, it is crucial to incorporate biomarkers to test target engagement or track disease progression in response to therapies, especially in rare diseases such as SCAs. In this article, we review the available rating scales and recent advances of biomarkers in CAG-repeat SCAs. We divided biomarkers into neuroimaging, body fluid, and physiological studies. Understanding the utility of each biomarker will facilitate the design of robust clinical trials to advance therapies for SCAs.

Automated summary

Spinocerebellar ataxias (SCAs) are a group of dominantly-inherited cerebellar ataxias, with CAG expansion-related SCAs being the most common. These diseases have high penetrance and defined disease progression, with emerging therapies being developed. Incorporating biomarkers into clinical trial design is crucial to test target engagement or track disease progression in response to therapies, especially in rare diseases such as SCAs.